3 PhD positions
INRIA has developed a strong expertise in mathematical modeling of biological systems with medical applications. Closely collaborating with clinicians in several renowned French and German hospitals and one of the best biology and toxicology institutes in Germany, it has been working on liver since many years, developing models of liver damage and regeneration, including tissue damage, blood flow and transport within the liver micro architecture. It is currently involved in different projects, among them the study of fibrosis and cirrhosis to help in clinical treatment development, the development of a bioengineered liver as well as the study of liver intoxication due to paracetamol.
In this context, we are looking for 3 PhD students for several complementary projects:

Project 1:

Image analysis and mathematical modeling of the micro-architectural changes of liver during development of liver fibrosis and cirrhosis.

Liver fibrosis and its succession state cirrhosis are diseases with increasing incidence. In close collaborations with biological and clinical teams in Germany the micro-architectural changes accompanied with these diseases will be analyzed, modeled using a spatial-temporal mathematical framework and simulated. As a second step, critical differences in the regeneration capacity of acute liver damage (e.g. by paracetamol/acetaminophen overdose or other injuries) in fibrosis and cirrhosis compared to healthy liver will be studied. Aims are to propose modeling-based treatment recommendations and strategies applicable in clinics.

Project 2:

Image analysis and mathematical modeling of a bioengineered liver.

Liver transplantation can be needed in case of acute liver failure or end-stage liver diseases such as cirrhosis. In this context, our team is involved in an ANR project aimed at developing liver replacements with the potential of transplantation into a patient. In close collaborations with clinicians in Paris region, biotechnologists and companies, mathematical models of the replacement tissues engineered will be developed to guide experiments, evaluate and predict the function of those tissues

Project 3:

Image analysis and multi-scale modeling of drug-induced liver injury.

Drug intoxication is one of the main causes of liver injury, with paracetamol intoxication being one of the main causes of acute liver failure. In collaboration with biologists and toxicologists in Germany, the impact of the drugs on liver architecture and function, in particular on the liver detoxification capacity will be studied. Drug-induced liver injury for several drugs will be studied within spatial temporal multi-scale models spanning molecular to body scale. The aim of this work is to propose models to better understand in details the multi-scale mechanisms in drug damage and subsequent organ regeneration.
Mathematical modeling aims at guiding experiments and clinical decision-making. In all projects, static or live images at histological scale of animal or human liver will be analyzed. The results are used to construct an in-silico multi-scale spatial-temporal liver model representing liver microarchitecture. Models may span molecular to tissue scales, implement molecular signaling and metabolism in each cell and whole tissues, as well as flow and transport systems.
The projects offer excellent opportunities to develop and advance both, image processing and analysis methods and chains as well as mechanistic computational models and software, and to use the computational tools to study highly relevant clinically, biotechnologically and pharmaceutically applications at the forefront of research. All those projects will be conducted in close collaboration with experimental and clinical partners, within a team of people with different key expertise with regard to image analysis and computational modeling.Depending on the main project focus, the background, expertise, and interests, employment either at INRIA in Paris, France or at IfADo, Dortmund, Germany, where our main experimental collaborator is localized would be possible.